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New “Hot Pocket” Geography May Point Toward Better Avian Flu Drugs

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Amid heightened concern over a possible epidemic of bird flu in humans, scientists in the United States and Taiwan are reporting critical new insights into the architecture of a key enzyme in the H5N1 avian influenza virus that enables the virus to spread. The report is scheduled for the June 20 issue of the Journal of the American Chemical Society, a weekly publication.

Rommie E. Amaro and colleagues focused on what has been termed the “hot pocket,” or more technically “the 150-loop.” This chain of amino acids forms a cavity in the neuraminidase enzyme that facilitates H5N1’s spread. Anti-flu drugs called neuraminidase inhibitors work by entering and binding to the hot pocket, almost like a hand fitting into a glove.

In the new study, researchers report that the hot pocket actually can have internal shapes substantially different than previously believed. That new structural understanding of the 150-loop could be valuable in efforts to design new and more effective anti-flu drugs, they state. Drugs capable of fitting more snugly into the cavity could yield a class of neuraminidase inhibitors that are more effective against H5N1-like flu viruses.

Progress toward development of a much-needed test for early detection of cancer of the urinary bladder — and for monitoring patients after treatment — is being reported in an article scheduled for the July 6 issue of ACS’ Journal of Proteome Research.

In the report, the University of Florida’s Steve Goodison and colleagues at the University of Michigan note that urinary bladder cancer is among the five most common malignancies worldwide. Early detection and treatment dramatically increases patient survival rates. However, the existing urinalysis test has serious drawbacks. “Consequently, the development of noninvasive urinalysis assays using reliable diagnostic markers would be of tremendous benefit to both patients and healthcare providers,” the report points out.

Their research identified potential biomarkers for bladder cancer, including a protein present in the urine of patients with bladder cancer but not other individuals. It is the same protein linked to liver and ovarian cancer in previous studies. Although the protein appears promising as a biomarker, the researchers cite the need for further studies in large groups of bladder cancer patients to determine its usefulness.

Protein-Enriched Milk May Reduce Need for Antibiotics in Animal Feed

The search for ways to promote growth of farm animals without adding antibiotics to feed has led scientists in Taiwan to an advance toward genetically engineering animals that produce higher levels of a natural growth-promoting protein in their milk.

In a study scheduled for publication in the June 13 issue of ACS’ Journal of Agricultural and Food Chemistry, a bi-weekly journal, Winston T. K. Cheng and colleagues point out that the protein, lactoferrin (LF), has anti-bacterial and anti-inflammatory actions and may serve as an alternative to antibiotics in agriculture. The researchers genetically engineered laboratory mice to produce milk enriched in pig LF, and studied the growth of 10 generations of mice pups fed on the milk. Mice fed LF-enriched milk grew 10-15 per cent faster than those fed on ordinary milk.

“In animal husbandry, it is thought that supplementing the diet of neonatal pigs with porcine LF may decrease mortality rates of piglets due to diarrhea and anemia by rendering them more resistant to common infectious agents,” the report states. “Transgenic animals expressing the LF protein in the mammary gland and secreting high levels of LF in the milk may be generated to produce a whole new herd of diarrhea- and anemia-resistant piglets with better growth performance and commercial value.”

A 4-year study of mercury in crude oil refined in the United States has found that, of the two major sources of U.S. fossil energy — mined coal and crude oil — crude oil contains much less toxic mercury, on average, than coal. The study is scheduled for publication in the July 1 issue of ACS’ Environmental Science & Technology, a semi-monthly journal.

S. Mark Wilhelm and colleagues point out that extensive studies had been done on mercury in coal, the nation’s other major fuel. Coal is the largest source of human-generated mercury emissions in the United States. Coal-fired power plants released about 48 tons of mercury annually, according to U. S. Environmental Protection Agency (EPA) data, a figure that would drop to 15 tons annually with implementation of new clean air regulations.

However, the amount of mercury present in crude oil, and thus potentially released into the air in automobile exhaust and other sources, remained uncertain due to a lack of accurate mercury concentration data for the wide range of crude oils produced domestically and imported into the U. S., the study noted.

To understand the mean concentration of mercury in oil processed by U.S. refineries, EPA employed two independent laboratories, each using different pre-qualified methods, to analyze oil streams arriving at U.S. refineries by tanker or pipeline. The samples included oil from the U. S. and 20 foreign countries. The total amount of mercury in crude oil processed in the U. S. annually is less than five percent of the amount contained in U. S. coal produced annually, the study concluded.

Concerns about Safety of Chinese Ingredients May Be Unwarranted When It Comes To Prescription Drugs

With Chinese manufacturers poised to increase exports of drug ingredients— and perhaps even begin shipping finished drug products—to the United States, an article in Chemical & Engineering News (C&EN), ACS’s weekly newsmagazine, questions allegations that foreign-made ingredients often are manufactured in factories that have never been inspected by the U. S. Food and Drug Administration (FDA).

The article, written by Jean-Franåois Tremblay, of C&EN’s Asia-Pacific Bureau, notes that concerns about counterfeit ingredients arose after recent scandals involving Chinese food and drug ingredients. In one incident, media reports said that an over-the-counter cough syrup formulated with a counterfeit Chinese ingredient killed dozens of people in Panama last November.

It is unlikely that counterfeit ingredients could reach prescription medicines sold in the United States because of the high degree of scrutiny that those ingredients receive in China and along their route to the pharmacy shelf, Tremblay reports. However, there is less scrutiny from FDA and other sources for over-the-counter or nonprescription ingredients. FDA only inspects the formulation facilities that make pills, syrups, and other finished products out of ingredients purchased from various suppliers, the article notes.

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Journal Information

Journal: Chemical & Engineering News

Journal Article: “Trusting medicine from China: Close FDA scrutiny of Chinese pharmaceutical ingredients extends only to those for prescription drugs”